आणविक और आनुवंशिक चिकित्सा

Treatment Outcomes and Toxicity Profile of Carfilzomib in Multiple Myeloma: A Single Institution Experience

Abstract

Thakur R, Nina Kohn and Brown MH

Carfilzomib is an irreversible proteasome inhibitor (PI), first approved in 2012 for treatment of relapsed refractory multiple myeloma (RRMM). The real-world use of carfilzomib in treatment of RRMM is important to assess. The objectives of this study are to evaluate the real-world outcome in overall response rates (ORR), progression-free survival (PFS), and adverse drug events (ADEs), including cardiotoxicity and nephrotoxicity for RRMM patients treated with carfilzomib. We retrospectively analyzed the charts of patients with a diagnosis of MM treated with carfilzomib between January 2013 and December 2018. Demographics, cytogenetics, fluorescence in situ hybridization (FISH), and treatment history were collected. Sixty-six patients fit the study criteria, with median age of 65 years (range 48 - 84). Using the Revised International Staging System (R-ISS), 7 (10.6%) patients were stage I, 28 (42.4%) stage II, and 31 (47.0%) stage III. Cytogenetics showed 33 (48.5%) were high risk. Eight (12.12%) patients were pretreated with more than 4 treatment lines and 27 (40.95) had an autologous stem cell transplant (ASCT) prior to carfilzomib. Prior treatments included lenalidomide, bortezomib, and cyclophosphamide-based regimens. The ORR was 77.2%, with 4 (6.2%) complete responses (CR). Ten patients (15%) received ASCT after carfilzomib for progression of disease (POD). The majority with POD received daratumumab (40%) or pomalidomide (46%). Grade 2 hypertension was noted in 9 (13.6%) patients, acute renal failure (ARF) in 11 (16.7%) and heart failure (HF) in 12 (18.2%). The median PFS on Carfilzomib was 6.96 months. This study showed carfilzomib improved PFS in patients with RRMM; however, there is increased risk for cardiac and renal toxicity, greater than previously reported in the literature. This study reinforces the importance for oncologists to be aware of these toxicities. Astute awareness, early monitoring, and prevention may favorably impact outcomes with use of carfilzomib.